BOS Is Associated With Decreased SIRT1 in Peripheral Blood Proinflammatory T, NK, and NKT-like Lymphocytes

Background. Immunosuppression therapy is ineffective at preventing chronic rejection of lung allografts (bronchiolitis obliterans syndrome [BOS]) and proinflammatory cytokines by steroid-resistant lymphocytes. The class III NAD-sirtuin 1 (SIRT1) is an important negative regulator of inflammation; however, SIRT1 activity following lung transplant has not been studied. We hypothesized that SIRT1 expression is decreased in proinflammatory lymphocytes following lung transplant and that treatment with SIRT1 activators (resveratrol, curcumin) and agents that prevent NAD depletion (theophylline) upregulate SIRT1 and reduce proinflammatory cytokine expression in these cells. Methods. Intracellular proinflammatory cytokines and SIRT1 were measured in blood T, natural killer T-like cell (NKT-like), and natural killer (NK) cells from patients with BOS (n = 10), stable lung transplant patients (n = 11), and healthy aged-matched controls (n = 10). Blood was cultured in the presence of ±25 µM resveratrol, ±1 µM curcumin, ±5 mg/L theophylline, ±1µM prednisolone and cytokines, and SIRT1 assessed using flow cytometry. Results. There was a loss of SIRT1 in T, NK-like, and NK cells in BOS patients compared with stable patients and controls (%CD8+ SIRT1+ T cells: 17 ± 10; 37 ± 10; 30 ± 10) (mean ± SEM BOS, stable, control, respectively) (P
Source: Transplantation - Category: Transplant Surgery Tags: Original Basic Science–General Source Type: research